Byssinosis is a disease of textile workers that is attributed to the action of cotton dust on the lung. The acute symptoms of byssinosis are accompanied by changes in lung function which indicate reversible narrowing of airways. The major compound(s) causing byssinosis are found in the cotton bracts and several hypotheses on the etiology of byssinosis have been advanced. The nonallergic release of histamine by an agent in cotton bracts perhaps is the most widely held hypothesis although endotoxins produced by bacterial contaminants also have been implicated in this disease. An antigen-antibody reaction has been reported to cause byssinosis but the proposed antigen in cotton bracts, a condensed tannin, was found to cause nonspecific precipitation of IgG in human sera. Thus, an immunological response was considered unlikely. However, we have found that this same tannin causes release of 5-HT and ADP from bovine and human platelets as well as aggregation of these platelets. Since 5-HT release and the mechanical events consequent to platelet aggregation reportedly cause bronchoconstriction, cotton bracts tannins might well alter pulmonary function through their effects on platelets. Aqueous extracts of cotton bracts have been reported to contract smooth muscle in a variety of isolated tissues including guinea-pig ileum and trachea. The byssinotic compound was not considered to be any known pharmacological agent since contractions were not blocked by classical receptor antagonists. In contrast, we have detected a bronchoactive agent in cotton bracts which causes powerful contractions of dog, cat, and baboon airways by activating 5-HT receptors. This compound, however, does not appear to be 5-HT. We propose to isolate and identify the bronchoactive factor and to determine its mechanism of action as well as that of the platelet active factor. These compounds might well be important in the pathogenesis of byssinosis and characterization of their mechanisms of action could foster new approaches to the management of this disease.